ABSTRACT
Vanishing white matter disease (VWM; MIM #603896), also known as childhood ataxia with central nervous system hypomyelination (CACH) syndrome, is an autosomal recessive transmitted leukoencephalopathy related to mutations in each of the 5 genes (EIF2B1, EIF2B2, EIF2B3, EIF2B4 and EIF2B5) encoding for the 5 subunits of eukaryotic translation initiation factor 2B (eIF2B), essential for protein synthesis. VWM is characterised by ataxia, spasticity, variable optic atrophy and intermittent episodes of acute regression of clinical and neurological status. Another key step in diagnosis, besides clinical picture and gene sequencing, is magnetic resonance imaging (MRI), which typically shows a progressive rarefaction of the brain white matter, and its replacement by cerebrospinal fluid (CSF). In the present paper we summarise the up-to-date knowledge about VWM and include the full list of known mutations.
Subject(s)
Brain Diseases/genetics , Brain Diseases/pathology , Eukaryotic Initiation Factor-2B/genetics , Hereditary Central Nervous System Demyelinating Diseases/genetics , Hereditary Central Nervous System Demyelinating Diseases/pathology , Mutation , Humans , Magnetic Resonance Imaging , Models, BiologicalABSTRACT
The authors describe an infant with vanishing white matter disease with demyelinating peripheral neuropathy. Sequence analysis of EIF2B5 gene showed that the patient was a double heterozygote, with novel missense mutation CGA-->CAA in codon 269 of exon 6, resulting in the replacement of an arginine residue with glutamine.
Subject(s)
Dementia, Vascular/diagnosis , Dementia, Vascular/genetics , Demyelinating Diseases/diagnosis , Demyelinating Diseases/genetics , Eukaryotic Initiation Factor-2B/genetics , Peripheral Nervous System Diseases/diagnosis , Peripheral Nervous System Diseases/genetics , Child, Preschool , Dementia, Vascular/complications , Demyelinating Diseases/complications , Genetic Predisposition to Disease/genetics , Humans , Male , Peripheral Nervous System Diseases/complicationsABSTRACT
BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a cause of hereditary cerebrovascular disease. It results from mutations in the Notch3 gene, a large gene with 33 exons. A cluster of mutations around exons 3 and 4 was originally reported and limited scanning of these exons was suggested for the diagnosis in most cases. OBJECTIVE: To report Notch3 mutation analysis in 28 unrelated Italian CADASIL families from central and south Italy. RESULTS: The highest rate of mutations was found in exon 11 (21%) and only 18% of mutations were in exon 4. This may be related to the peculiar distribution of Notch3 mutations in the regions of origin of the families. CONCLUSIONS: The results suggest that limited scanning of exons 3 and 4 is inadvisable in CADASIL cases of Italian origin.
